The Argentina international hit the milestone with the second goal in a 2-0 Liga victory over Valencia at the weekend, reaching the quadruple century in his 471st appearance.
"Messi is in top condition," said Luis Enrique. "400 goals? That's almost impossible. Unrepeatable I would say."
Messi, who surpassed Paulino Alcantara as Barca's all-time leading scorer last season, has broken a host of records this term.
In November, he struck a hat-trick against Sevilla to overhaul Telmo Zarra's previous best La Liga goals mark of 251. Messi's La Liga numbers now come in at 278 goals in 309 matches.
During the same month he surpassed Real Madrid great Raul as the UEFA Champions League's all-time top goalscorer, although he now lies level with great rival Cristiano Ronaldo on 75.
When Messi took home the matchball against Rayo Vallecano in March it was his 32nd hat-trick - passing another of former Athletic Bilbao striker Zarra's Spanish records.
Barcelona host Paris Saint-Germain in the second leg of their Champions League quarter-final on Tuesday, leading 3-1 from the away leg.
